In the past year, the scientific program in the newly organized Molecular Virology Section of LMM has focused on three broad areas. These encompass: I) Molecular Regulation of HIV-1; II) Molecular Regulation of HTLV-I; and III) Molecular applications relevant for the development of HIV-1 specific ribozymes and transdominant/attenuated human immunodeficiency viruses. Here in a short format, it is not possible to present comprehensively our accomplishments over the past year. Details of our research can be better appreciated from the annual bibliography. However, we can capsulize our progress in 1993- 1994 with the following 11 points. Selected findings from our research program include: 1) Understanding crucial interactions between Sp1 and HIV-1 Tat; 2) Obtaining evidence that HIV-1 expression is influenced by integration and replication; 3) Demonstrating that the second exon of Tat contributes to optimal expression from the viral LTR; 4) Providing evidence that Tat has a novel function in viral infectivity; 5) Elucidating the activation of cellular RNA-binding proteins in response to DNA-damaging events; 6) Identifying the human autoantigen La as a novel TAR RNA-binding protein; 7) Mapping the expressed gene of TAR RNA-binding protein (TRBP) to human chromosome 12 and mouse chromosome 15; 8) Delineating the minimal activation domain in the HTLV-I transactivator, Tax; 9) Characterizing interactions between Tax and tumor suppressor p53; 10) Constructing expression competent Rev(-) HIV-1 for use as a possible live-attenuated vaccine; and 11) Quantitating the intracellular efficiencies of five ribozymes targeted to separate loci in the HIV-1 genome. Additional examples of studies that are ongoing and have yet reached "critical mass" include 1) developing through mutagenesis a minimally active ribozyme for HIV-1; 2) studying the roles of PKR in suppressing HIV-1 mRNA translation; 3) creating HIV-1 infectious genomes that could be treated with ganciclovir; 4) selecting for novel cellular factors that binds HIV-1 regulatory proteins using the yeast two- hybrid system; 5) engineering human parvovirus Rep gene product as a dominant suppressor of HIV-1 replication; 6) analyzing cellular genes that are induced by Tat using differential display technology; 7) selecting in vivo for more efficient Tat gene products.